Vocal Cord Paralysis UnilateralNCT03790956
Silk Protein Microparticle-based Filler for Injection Augmentation
A study testing Silk Microparticle Filler Injection in people with Vocal Cord Paralysis Unilateral and Dysphonia, run by University of Southern California at 1 site in United States.
Trial summary
This study will investigate the safety and efficacy of a silk protein microparticle-based filler for vocal fold injection augmentation to treat dysphonia/dysphagia secondary to vocal fold paralysis. Participants will receive one injection and follow-up for a planned period of 12 months. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Vocal Cord Paralysis Unilateral, Dysphonia, Dysphagia, Oropharyngeal
- What is being tested?
- Silk Microparticle Filler Injection
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2020to 15 Mar 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Unilateral vocal fold immobility with glottal insufficiency present for at least 2 weeks from onset
- Willingness to partake in study and follow-up as documented by signed informed consent
Who cannot join
- History of allergy/hypersensitivity to silk or silk containing products
- History of allergy/hypersensitivity to hyaluronic acid (HA) or HA containing products
- History of allergy/hypersensitivity to lidocaine or amide-based anesthetics
- History of an autoimmune condition
- Significant immunocompromised state (i.e. immunosuppression s/p transplantation)
- Pregnancy
Show all 10Show fewer
- Active infection or inflammation in the larynx
- Comorbid known laryngeal conditions including but not limited to vocal fold scar, vocal tremor, laryngeal dystonia, etc. that would warrant other interventions for optimal treatment
- History of laryngeal surgery
- Life expectancy of less than 6 months
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Southern California
Los Angeles, California, 90033
About this study
Official title: Safety and Efficacy of a Silk Protein Microparticle-based Filler for Injection Augmentation in Treating Unilateral Vocal Fold Paralysis
This study will investigate the safety and efficacy of a silk protein microparticle-based filler for vocal fold injection augmentation to treat dysphonia/dysphagia secondary to vocal fold paralysis. Participants will receive one injection and follow-up for a planned period of 12 months.
Read the detailed description
Vocal fold paralysis is a clinical condition that arises commonly as a complication of surgery, endotracheal intubation, malignancy, or idiopathic etiologies. It often results in glottal insufficiency, which is the inability of the true vocal folds to meet and achieve complete closure during normal physiologic functions such as speech, swallowing, and coughing. The presence of vocal fold paralysis with glottal insufficiency can lead to decreased quality-of-life, as well as increase risks of complications such as aspiration pneumonia.
Current treatments for vocal fold paralysis are based around techniques to medialize the paralyzed vocal fold. One manner in which this is done is via injection of a filler or bulking agent into the vocal fold in order to augment it. Injection augmentation has many advantages including its minimally invasive nature, overall safety and low risk/complication rate, immediate clinical effect, and ability to perform it at the bedside or in-office. Various materials are used for injection augmentation including autologous fat, hyaluronic acid, collagen, carboxymethylcellulose, and calcium hydroxyapatite. However, all of the current injection choices have individual limitations such as temporary effect, unpredictability due to variable resorption by the body, unfavorable mechanical properties, and challenging handling attributes.
Silk is derived from the Bombyx mori silk worm and has a long history as a surgical biomaterial. Surgical scaffolds derived from silk have been used for reconstructive surgery, due to its ability to allow cellular infiltration and encourage tissue regeneration/remodeling. Given the potential advantages of such a material, Brown et al engineered and studied a novel silk protein microparticle-based filler material suitable for injection augmentation.
Patients with unilateral vocal fold paralysis identified at the study sites will be offered participation in this study to receive injection augmentation of the paralyzed vocal fold with the filler material under investigation. Outcome measures evaluated pre- and post-injection and over follow-up visits will include various patient reported quality of life indices, objective clinical assessments of voice, laryngeal videostroboscopy examinations, and acoustic/aerodynamic testing. The investigators hypothesize that the novel silk protein microparticle-based filler will have a favorable safety profile for use as an injectable material in the human larynx and it will produce durable clinical benefit lasting up to 12 months.
- Being tested
- Silk Microparticle Filler Injection
- Keywords
- vocal fold paralysis, glottal insufficiency, vocal fold injection, augmentation, medialization, laryngoplasty, silk
- Medical subject headings
- Vocal Cord Paralysis, Dysphonia, Deglutition Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Silk Microparticle Filler InjectionProcedure or surgery
A silk protein microparticle-based filler will be injected deep to the thyroarytenoid muscle of the paralyzed vocal fold to augment/medialize its position.
| Study group | Role | What they receive |
|---|---|---|
| Silk Microparticle Filler Injection | Experimental | A silk protein microparticle-based filler will be injected deep to the thyroarytenoid muscle of the paralyzed vocal fold to augment/medialize its position. Receives: Procedure: Silk Microparticle Filler Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events as assessed by FDA/CBER Adverse Event Severity Grading Scale
Adverse event severity grading scale from 1 to 4, with grade 1 as mild, grade 2 as moderate, grade 3 as severe, and grade 4 potentially life-threatening.
Measured: 12 months
Secondary outcomes (14)
Quality of Life as assessed by Voice Handicap Index-10 (VHI-10)
VHI-10 is a patient questionnaire with 10 statements rated from 0 to 4 with overall scale 0-40.
Measured: 12 months
Quality of Life as assessed by Vocal Fatigue Index (VFI)
VFI is a patient questionnaire with 19 statements rated from 0-4 with overall scale 0-76.
Measured: 12 months
Quality of Life as assessed by Dyspnea Index (DI)
DI is a patient questionnaire with 10 statements rated from 0 to 4 with overall scale 0-40.
Measured: 12 months
Quality of Life as assessed by Eating Assessment Tool (EAT-10)
EAT-10 is a patient questionnaire with 10 statements rated from 0 to 4 with overall scale 0-40.
Measured: 12 months
Objective Vocal Quality as assessed by experts using the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) instrument
Blinded evaluations of audio voice recordings will be performed by laryngologists and speech-language pathologists using the CAPE-V, which grades overall severity, roughness, breathiness, strain, pitch, and loudness from 0-100.
Measured: 12 months
Vocal Fold Appearance as assessed by experts using a modified version of the Voice-Vibratory Assessment with Laryngeal Imaging (VALI) form
Blinded assessments of recorded laryngeal videostroboscopy exams will be performed by laryngologists and speech-language pathologists using a modified version of the VALI, which is a graphical rating form to grade various components seen on stroboscopy.
Measured: 12 months
Objective Acoustic Testing as assessed by fundamental frequency
Measurement of fundamental frequency (F0) during sustained vowel phonation.
Measured: 12 months
Objective Acoustic Testing as assessed by Sound Pressure Level (SPL)
Measurement of minimum/maximum SPL during phonation.
Measured: 12 months
Objective Acoustic Testing as assessed by Cepstral Peak Prominence (CPP)
Measurement of CPP during phonation.
Measured: 12 months
Objective Aerodynamic Testing as assessed by Vital Capacity (VC)
Measurement of VC.
Measured: 12 months
Objective Aerodynamic Testing as assessed by Maximum Phonation Time (MPT)
Measurement of MPT.
Measured: 12 months
Objective Aerodynamic Testing as assessed by Mean Glottal Flow Rate (MGFR)
Measurement of MGFR.
Measured: 12 months
Objective Aerodynamic Testing as assessed by Subglottal Pressure (SGP)
Measurement of SGP.
Measured: 12 months
Objective Aerodynamic Testing as assessed by Cough Velocity (CV)
Measurement of maximum CV.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jan 2019
- Study start1 Jul 2020
- Primary completion15 Mar 2023
- Study completion15 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Vocal Cord Paralysis UnilateralStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single vocal fold injection of study material with possible booster injection, and follow-up of 12 months post injection.
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Southern California
- Sponsor type
- University, hospital or other
- Collaborators
- Sofregen Medical, Inc.
- Responsible party
- Principal investigator, Michael Johns, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03790956
- Sponsor's protocol ID
- APP-18-05229
- Status last verified
- May 2023
- First submitted
- 25 Nov 2018
- Last updated
- 10 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Spector BC, Netterville JL, Billante C, Clary J, Reinisch L, Smith TL. Quality-of-life assessment in patients with unilateral vocal cord paralysis. Otolaryngol Head Neck Surg. 2001 Sep;125(3):176-82. doi: 10.1067/mhn.2001.117714.
PubMed 11555751Brown JE, Gulka CP, Giordano JEM, Montero MP, Hoang A, Carroll TL. Injectable Silk Protein Microparticle-based Fillers: A Novel Material for Potential Use in Glottic Insufficiency. J Voice. 2019 Sep;33(5):773-780. doi: 10.1016/j.jvoice.2018.01.017. Epub 2018 Mar 30.
PubMed 29609905Etienne O, Schneider A, Kluge JA, Bellemin-Laponnaz C, Polidori C, Leisk GG, Kaplan DL, Garlick JA, Egles C. Soft tissue augmentation using silk gels: an in vitro and in vivo study. J Periodontol. 2009 Nov;80(11):1852-8. doi: 10.1902/jop.2009.090231.
PubMed 19905955Bellas E, Panilaitis BJ, Glettig DL, Kirker-Head CA, Yoo JJ, Marra KG, Rubin JP, Kaplan DL. Sustained volume retention in vivo with adipocyte and lipoaspirate seeded silk scaffolds. Biomaterials. 2013 Apr;34(12):2960-8. doi: 10.1016/j.biomaterials.2013.01.058. Epub 2013 Jan 29.
PubMed 23374707Kijanska M, Marmaras A, Hegglin A, Kurtcuoglu V, Giovanoli P, Lindenblatt N. In vivo characterization of the integration and vascularization of a silk-derived surgical scaffold. J Plast Reconstr Aesthet Surg. 2016 Aug;69(8):1141-50. doi: 10.1016/j.bjps.2016.01.017. Epub 2016 Feb 5.
PubMed 26966076Rosen CA, Gartner-Schmidt J, Casiano R, Anderson TD, Johnson F, Remacle M, Sataloff RT, Abitbol J, Shaw G, Archer S, Zraick RI. Vocal fold augmentation with calcium hydroxylapatite: twelve-month report. Laryngoscope. 2009 May;119(5):1033-41. doi: 10.1002/lary.20126.
PubMed 19274731
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of a Silk Protein Microparticle-based Filler for Injection Augmentation in Treating Unilateral Vocal Fold Paralysis
- ClinicalTrials.gov ID
- NCT03790956
- Acronym / sponsor ID
- APP-18-05229
- Keywords
- vocal fold paralysis, glottal insufficiency, vocal fold injection, augmentation, medialization, laryngoplasty, silk
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University of Southern CaliforniaUniversity, hospital or other
- Collaborators
- Sofregen Medical, Inc.
- Study start
- 1 Jul 2020 (actual)
- Primary completion
- 15 Mar 2023 (actual)
- Study completion
- 15 Mar 2023 (actual)
- First posted
- 2 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will investigate the safety and efficacy of a silk protein microparticle-based filler for vocal fold injection augmentation to treat dysphonia/dysphagia secondary to vocal fold paralysis. Participants will receive one injection and follow-up for a planned period of 12 months.
Detailed description
Vocal fold paralysis is a clinical condition that arises commonly as a complication of surgery, endotracheal intubation, malignancy, or idiopathic etiologies. It often results in glottal insufficiency, which is the inability of the true vocal folds to meet and achieve complete closure during normal physiologic functions such as speech, swallowing, and coughing. The presence of vocal fold paralysis with glottal insufficiency can lead to decreased quality-of-life, as well as increase risks of complications such as aspiration pneumonia.
Current treatments for vocal fold paralysis are based around techniques to medialize the paralyzed vocal fold. One manner in which this is done is via injection of a filler or bulking agent into the vocal fold in order to augment it. Injection augmentation has many advantages including its minimally invasive nature, overall safety and low risk/complication rate, immediate clinical effect, and ability to perform it at the bedside or in-office. Various materials are used for injection augmentation including autologous fat, hyaluronic acid, collagen, carboxymethylcellulose, and calcium hydroxyapatite. However, all of the current injection choices have individual limitations such as temporary effect, unpredictability due to variable resorption by the body, unfavorable mechanical properties, and challenging handling attributes.
Silk is derived from the Bombyx mori silk worm and has a long history as a surgical biomaterial. Surgical scaffolds derived from silk have been used for reconstructive surgery, due to its ability to allow cellular infiltration and encourage tissue regeneration/remodeling. Given the potential advantages of such a material, Brown et al engineered and studied a novel silk protein microparticle-based filler material suitable for injection augmentation.
Patients with unilateral vocal fold paralysis identified at the study sites will be offered participation in this study to receive injection augmentation of the paralyzed vocal fold with the filler material under investigation. Outcome measures evaluated pre- and post-injection and over follow-up visits will include various patient reported quality of life indices, objective clinical assessments of voice, laryngeal videostroboscopy examinations, and acoustic/aerodynamic testing. The investigators hypothesize that the novel silk protein microparticle-based filler will have a favorable safety profile for use as an injectable material in the human larynx and it will produce durable clinical benefit lasting up to 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single vocal fold injection of study material with possible booster injection, and follow-up of 12 months post injection.
| Arm | Type | Receives |
|---|---|---|
| Silk Microparticle Filler Injection | Experimental | Procedure: Silk Microparticle Filler InjectionA silk protein microparticle-based filler will be injected deep to the thyroarytenoid muscle of the paralyzed vocal fold to augment/medialize its position. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Unilateral vocal fold immobility with glottal insufficiency present for at least 2 weeks from onset
- Willingness to partake in study and follow-up as documented by signed informed consent
Key exclusion criteria (10 listed)
- History of allergy/hypersensitivity to silk or silk containing products
- History of allergy/hypersensitivity to hyaluronic acid (HA) or HA containing products
- History of allergy/hypersensitivity to lidocaine or amide-based anesthetics
- History of an autoimmune condition
- Significant immunocompromised state (i.e. immunosuppression s/p transplantation)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Silk Microparticle Filler InjectionA silk protein microparticle-based filler will be injected deep to the thyroarytenoid muscle of the paralyzed vocal fold to augment/medialize its position. | Procedure or surgery | Silk Microparticle Filler Injection |
Primary outcome
Incidence of Treatment-Emergent Adverse Events as assessed by FDA/CBER Adverse Event Severity Grading Scale
Time frame: 12 months
Adverse event severity grading scale from 1 to 4, with grade 1 as mild, grade 2 as moderate, grade 3 as severe, and grade 4 potentially life-threatening.
14 secondary outcomes
Quality of Life as assessed by Voice Handicap Index-10 (VHI-10)
Time frame: 12 months
Quality of Life as assessed by Vocal Fatigue Index (VFI)
Time frame: 12 months
Quality of Life as assessed by Dyspnea Index (DI)
Time frame: 12 months
Quality of Life as assessed by Eating Assessment Tool (EAT-10)
Time frame: 12 months
Objective Vocal Quality as assessed by experts using the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) instrument
Time frame: 12 months
Vocal Fold Appearance as assessed by experts using a modified version of the Voice-Vibratory Assessment with Laryngeal Imaging (VALI) form
Time frame: 12 months
Objective Acoustic Testing as assessed by fundamental frequency
Time frame: 12 months
Objective Acoustic Testing as assessed by Sound Pressure Level (SPL)
Time frame: 12 months
Objective Acoustic Testing as assessed by Cepstral Peak Prominence (CPP)
Time frame: 12 months
Objective Aerodynamic Testing as assessed by Vital Capacity (VC)
Time frame: 12 months
Objective Aerodynamic Testing as assessed by Maximum Phonation Time (MPT)
Time frame: 12 months
Objective Aerodynamic Testing as assessed by Mean Glottal Flow Rate (MGFR)
Time frame: 12 months
Objective Aerodynamic Testing as assessed by Subglottal Pressure (SGP)
Time frame: 12 months
Objective Aerodynamic Testing as assessed by Cough Velocity (CV)
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2023.
- Background: PubMed 11555751Spector BC, Netterville JL, Billante C, Clary J, Reinisch L, Smith TL. Quality-of-life assessment in patients with unilateral vocal cord paralysis. Otolaryngol Head Neck Surg. 2001 Sep;125(3):176-82. doi: 10.1067/mhn.2001.117714.
- Background: PubMed 29609905Brown JE, Gulka CP, Giordano JEM, Montero MP, Hoang A, Carroll TL. Injectable Silk Protein Microparticle-based Fillers: A Novel Material for Potential Use in Glottic Insufficiency. J Voice. 2019 Sep;33(5):773-780. doi: 10.1016/j.jvoice.2018.01.017. Epub 2018 Mar 30.
- Background: PubMed 19905955Etienne O, Schneider A, Kluge JA, Bellemin-Laponnaz C, Polidori C, Leisk GG, Kaplan DL, Garlick JA, Egles C. Soft tissue augmentation using silk gels: an in vitro and in vivo study. J Periodontol. 2009 Nov;80(11):1852-8. doi: 10.1902/jop.2009.090231.
- Background: PubMed 23374707Bellas E, Panilaitis BJ, Glettig DL, Kirker-Head CA, Yoo JJ, Marra KG, Rubin JP, Kaplan DL. Sustained volume retention in vivo with adipocyte and lipoaspirate seeded silk scaffolds. Biomaterials. 2013 Apr;34(12):2960-8. doi: 10.1016/j.biomaterials.2013.01.058. Epub 2013 Jan 29.
- Background: PubMed 26966076Kijanska M, Marmaras A, Hegglin A, Kurtcuoglu V, Giovanoli P, Lindenblatt N. In vivo characterization of the integration and vascularization of a silk-derived surgical scaffold. J Plast Reconstr Aesthet Surg. 2016 Aug;69(8):1141-50. doi: 10.1016/j.bjps.2016.01.017. Epub 2016 Feb 5.
- Background: PubMed 19274731Rosen CA, Gartner-Schmidt J, Casiano R, Anderson TD, Johnson F, Remacle M, Sataloff RT, Abitbol J, Shaw G, Archer S, Zraick RI. Vocal fold augmentation with calcium hydroxylapatite: twelve-month report. Laryngoscope. 2009 May;119(5):1033-41. doi: 10.1002/lary.20126.
- Individual participant dataSharing planned: Undecided
Related trials for Vocal Cord Paralysis Unilateral
Not yet recruiting
Recurrent Laryngeal Nerve Monitoring During Pediatric Aerodigestive Tract and Cardiac Surgery
Unilateral Vocal Cord Paralysis, Unilateral Vocal Cord Paresis
Enrolling by invitationObservational study
Outcomes Tracking in Unilateral Vocal Fold Paralysis (UVFP) and Atrophy After Medialization Laryngeal Surgery
Unilateral Vocal Cord Paralysis, Vocal Cord Atrophy
Active, not recruiting
Performance of the SPIRION Laryngeal Pacemaker in BVFP Patients Without Glottal Enlargement
Bilateral Vocal Cord Paralysis
Recruiting
APrevent-VOIS-Implant-002 - a Two-Part, Open-Label, Non-Randomized Multicenter Study
Paralysis, Unilateral, Vocal Cord
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Silk Microparticle Filler Injection in people with Vocal Cord Paralysis Unilateral and Dysphonia, run by University of Southern California at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events as assessed by FDA/CBER Adverse Event Severity Grading Scale (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03790956, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2023.